[Federal Register Volume 63, Number 196 (Friday, October 9, 1998)]
[Rules and Regulations]
[Pages 54352-54353]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-27080]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 556 and 558


New Animal Drugs For Use In Animal Feeds; Ivermectin

AGENCY:  Food and Drug Administration, HHS.

ACTION:  Final rule.

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SUMMARY:  The Food and Drug Administration (FDA) is amending the animal 
drug regulations to reflect approval of a supplemental new animal drug 
application (NADA) filed by Merial Ltd. The supplemental NADA provides 
for use of ivermectin Type A medicated articles to make Type B and C 
medicated swine feeds, to make Type C feed for treatment and control of 
threadworms (Strongyloides ransomi), and as top-dressing for individual 
treatment of adult swine.

EFFECTIVE DATE:  October 9, 1998.

FOR FURTHER INFORMATION CONTACT:  Estella Z. Jones, Center for 
Veterinary Medicine (HFV-135), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-594-1643.

SUPPLEMENTARY INFORMATION:  Merial Ltd., 2100 Ronson Rd., Iselin, NJ 
08830-3077, is sponsor of NADA 140-974 that provides for use of Ivomec 
(ivermectin 0.6%) Type A articles to make ivermectin Type B and C swine 
feeds. The Type C feeds contain 1.8 grams ivermectin per ton for 
feeding to weaned, growing and finishing swine, and adult and breeding 
swine. It is used for treatment and control of gastrointestinal 
roundworm, kidney worm, and lungworm infections, and lice and mite 
infestations. The supplemental NADA provides for use of the Type C 
feeds for treatment and control of threadworms (Strongyloides ransomi) 
infections, specifically treatment and control of ``threadworms 
(Strongyloides ransomi, adults and somatic larvae, and prevention of 
transmission of infective larvae to piglets, via the colostrum or milk, 
when fed during gestation),'' and for use as top-dressing for 
individual treatment of adult swine. The supplemental NADA is approved 
as of August 10, 1998, and the regulations are amended in Sec. 558.300 
(21 CFR 558.300) to reflect the approval. The basis of approval is 
discussed in the freedom of information summary.
    In addition, Sec. 558.300 is amended by redesignating paragraph (c) 
as paragraph (d), adding new paragraph (c), and in newly redesignated 
paragraph (d) inserting several editorial and technical changes and 
adding a required limitation statement.
    This supplemental NADA is for use of approved ivermectin Type A 
medicated articles to make Type B and C medicated feeds. Ivermectin is 
a Category II drug as defined in 21 CFR 558.3(b)(1)(ii). As provided in 
21 CFR 558.4(b), an approved medicated feed application is required for 
making Type B or C medicated feeds as in this application. Under 
section 512(m) of the Federal Food, Drug, and Cosmetic Act as amended 
by the Animal Drug Availability Act of 1996 (Pub. L. 104-250), 
medicated feed applications have been replaced by the requirement for 
feed mill licenses. Therefore, use of ivermectin Type A medicated 
articles to make Type B and C medicated feeds as provided in this NADA 
is limited to manufacture in a licensed feed mill.
    Also, the regulation concerning tolerances for ivermectin residues 
in edible tissues is amended to provide for an acceptable daily intake 
(ADI) for total ivermectin residues. The ADI is the amount of total 
drug residue that can be safely consumed by humans every day. 
Previously, FDA had codified safe concentrations for drug residues. The 
safe concentrations were confusing because few individuals understood 
the relationship between safe concentrations, a value representing 
total residues, and tolerances, the part of the drug residue in a given 
tissue that is detected by a specific analytical method. To eliminate 
this confusion, FDA is codifying the ADI.
    In addition, the regulations for tolerances for ivermectin residues 
is further amended to establish a tolerance for ivermectin residues in 
swine muscle.
    In accordance with the freedom of information provisions of 21 CFR 
part 20 and 514.11(e)(2)(ii), a summary of safety and effectiveness 
data and information submitted to support approval of this supplemental 
application may be seen in the Dockets Management Branch (HFA-305), 
Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, 
MD 20852, between 9 a.m. and 4 p.m., Monday through Friday.
    Under section 512(c)(2)(F)(iii) of the Federal Food, Drug, and 
Cosmetic Act, this supplemental approval qualifies for 3 years of 
marketing exclusivity beginning August 10, 1998, because the 
supplemental application contains substantial evidence of the 
effectiveness of the drug involved, any studies of animal safety or, in 
the case of food-producing animals, human food safety studies (other 
than bioequivalence or residue studies) required for approval of the 
supplement and conducted or sponsored by the applicant. The 3 years of 
marketing exclusivity applies only to use in swine for treatment and 
control of threadworms (Strongyloides ransomi, adults and somatic 
larvae, and prevention of transmission of infective larvae to piglets, 
via the colostrum or milk, when fed during gestation).
    FDA has determined under 21 CFR 25.33(a)(1) and (a)(7) that this 
action is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.

List of Subjects

 21 CFR Part 556

     Animal drugs, Foods.

21 CFR Part 558

     Animal drugs, Animal feeds.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs and 
redelegated to the Center for Veterinary Medicine, 21 CFR parts 556 and 
558 are amended as follows:

PART 556--TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD

    1. The authority citation for 21 CFR part 556 continues to read as 
follows:

    Authority:  21 U.S.C. 342, 360b, 371.

    2. Section 556.344 is revised to read as follows:


Sec. 556.344   Ivermectin.

    (a) Acceptable daily intake (ADI). The ADI for total residues of 
ivermectin is 1 microgram per kilogram of body weight per day.
    (b) Tolerances--(1) Liver. A tolerance is established for 22,23-
dihydroavermectin B1a (marker residue) in liver (target 
tissue) as follows:
    (i) Cattle. 100 parts per billion.

[[Page 54353]]

    (ii) Swine. 20 parts per billion.
    (iii) Sheep. 30 parts per billion.
    (iv) Reindeer. 15 parts per billion.
    (v) American bison. 15 parts per billion.
    (2) Muscle. Muscle residues are not indicative of the safety of 
other edible tissues. A tolerance is established for 22,23-
dihydroavermectin B1a (marker residue) in muscle as follows:
    (i) Swine. 20 parts per billion.
    (ii) [Reserved]

PART 558--NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS

    3. The authority citation for 21 CFR part 558 continues to read as 
follows:

    Authority:  21 U.S.C. 360b, 371.

    4. Section 558.300 is amended by redesignating paragraph (c) as 
paragraph (d), by adding new paragraph (c) and reserving it, by adding 
introductory text to newly redesignated paragraph (d), and by revising 
newly redesignated paragraph (d)(1), to read as follows:


Sec. 558.300   Ivermectin.

* * * * *
    (c) [Reserved]
    (d) Conditions of use. It is used in swine feed as follows:
    (1) Amount per ton. For weaned, growing-finishing swine, feed 1.8 
grams of ivermectin (to provide 0.1 milligram per kilogram of body 
weight per day). For adult and breeding swine, feed 1.8 to 11.8 grams 
of ivermectin (to provide 0.1 milligram per kilogram of body weight per 
day). For adult and breeding swine, may be top-dressed on daily ration 
for individual treatment at levels of 18.2 to 1180 grams (to provide 
0.1 milligram per kilogram of body weight per day).
    (i) Indications for use. For treatment and control of 
gastrointestinal roundworms (Ascaris suum, adults and fourth-stage 
larvae; Ascarops strongylina, adults; Hyostrongylus rubidus, adults and 
fourth-stage larvae; Oesophagostomum spp., adults and fourth-stage 
larvae); kidneyworms (Stephanurus dentatus, adults and fourth-stage 
larvae); lungworms (Metastrongylus spp., adults); threadworms 
(Strongyloides ransomi, adults and somatic larvae, and prevention of 
transmission of infective larvae to piglets, via the colostrum or milk, 
when fed during gestation); lice (Haematopinus suis); and mange mites 
(Sarcoptes scabiei var. suis).
    (ii) Limitations. For use in swine feed only. Feed as sole ration 
for 7 consecutive days. Withdraw 5 days before slaughter. Consult your 
veterinarian for assistance in the diagnosis, treatment, and control of 
parasitism.
* * * * *

    Dated: September 28, 1998.
 Margaret Ann Miller,
 Acting Director, Office of New Animal Drug Evaluation, Center for 
Veterinary Medicine.
[FR Doc. 98-27080 Filed 10-8-98; 8:45 am]
BILLING CODE 4160-01-F